The objective of this study is to determine in subjects heterozygous for familial hypercholesterolemia (FH) whether the very massive reduction in plasma total and low density lipoprotein cholesterol (approximately 120 mg/dl) which can be achieved using repetitive isovolumetric plasma exchange (RPE) coupled with hypocholesterolemic drug therapy can induce regression or prevent progression of atheromatous coronary artery disease. The substantial decrease and improved long term control of low density lipoprotein cholesterol by RPE coupled with hypocholesterolemic drugs should amplify the preliminary evidence which has indicated that regression of early femoral atherosclerosis and nonprogression of advanced coronary lesions can be achieved by drug treatment alone in heterozygous FH. We propose to undertake long-term (four years) RPE at two week intervals in fifteen heterozygous subjects with FH. Pretreatment and within treatment coronary atheromatous lesions and ventricular function and perfusion will be assessed by serial quantitative, computerized coronary angiography, rest and exercise Thallium-201 perfusion studies, respectively. The effectiveness of RPE will be judged not only by longitudinal studies of the plasma exchange group, but also in a randomized concurrent control group of subjects receiving only maximal drug therapy. In addition, comparison will also be made against two groups of patients (historical controls) selected by Dr. John Brensike from the type II coronary intervention study recently completed at the NIH. These patients will be selected using the same criteria for entry into this study and will have been treated with diet alone or diet plus cholestyramine. The subjects will have undergone cardiac catheterization at the start of the study, at two years after entry, and at five years after entry. In effect, therefore, the results of repeat coronary angiography in fifteen patients who undergo massive reductions in plasma cholesterol by REP plus maximal drug therapy will be compared to three control groups: a randomized concurrently treated group (diet plus maximal drug therapy), and two historical NIH concurrently treated groups (one with dietary treatment only, and a group on diet plus cholestyramine).